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Record W2980263829 · doi:10.1113/ep088058

Influence of methazolamide on the human control of breathing: A comparison to acetazolamide

2019· article· en· W2980263829 on OpenAlexafffund
Luc J. Teppema, Lindsey M. Boulet, Heather Hackett, Paolo B. Dominelli, William S. Cheyne, Giulio S. Dominelli, Erik R. Swenson, Glen E. Foster

Bibliographic record

VenueExperimental Physiology · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHigh Altitude and Hypoxia
Canadian institutionsKelowna General HospitalUniversity of British Columbia, Okanagan CampusUniversity of British ColumbiaUniversity of WaterlooInterior Health
FundersNatural Sciences and Engineering Research Council of CanadaMichael Smith Health Research BCCanada Foundation for Innovation
KeywordsAcetazolamideBreathingMedicineChemistryAnesthesiaInternal medicineCardiology

Abstract

fetched live from OpenAlex

New Findings What is the central question of this study? Acetazolamide and methazolamide both reduce hypoxic pulmonary vasoconstriction equally, but methazolamide does not impair skeletal muscle function. The effect of methazolamide on respiratory control in humans is not yet known. What is the main finding and its importance? Similar to acetazolamide after chronic oral administration, methazolamide causes a metabolic acidosis and shifts the ventilatory CO 2 response curve leftwards without reducing O 2 sensitivity. The change in ventilation over the change in log provides a more accurate measure of hypoxic sensitivity than the change in ventilation over the change in arterial oxyhaemoglobin saturation. Abstract Acetazolamide is used to prevent/treat acute mountain sickness and both central and obstructive sleep apnoea. Methazolamide, like acetazolamide, reduces hypoxic pulmonary vasoconstriction, but has fewer side‐effects, including less impairment of skeletal muscle function. Given that the effects of methazolamide on respiratory control in humans are unknown, we compared the effects of oral methazolamide and acetazolamide on ventilatory control and determined the ventilation–log relationship in humans. In a double‐blind, placebo‐controlled, randomized cross‐over design, we studied the effects of acetazolamide (250 mg three times daily), methazolamide (100 mg twice daily) and placebo in 14 young male subjects who were exposed to 7 min of normoxic hypercapnia and to three levels of eucapnia and hypercapnic hypoxia. With placebo, methazolamide and acetazolamide, the CO 2 sensitivities were 2.39 ± 1.29, 3.27 ± 1.82 and 2.62 ± 1.79 l min −1 mmHg −1 (n.s.) and estimated apnoeic thresholds 32 ± 3, 28 ± 3 and 26 ± 3 mmHg, respectively ( P < 0.001, placebo versus methazolamide and acetazolamide). The relationship between ventilation ( ) and log (using arterialized venous in hypoxia) was linear, and neither agent influenced the relationship between hypoxic sensitivity ( ) and arterial [H + ]. Using rather than Δ /Δ arterial oxyhaemoglobin saturation enables a more accurate estimation of oxygenation and ventilatory control in metabolic acidosis/alkalosis when right‐ or leftward shifts of the oxyhaemoglobin saturation curve occur. Given that acetazolamide and methazolamide have similar effects on ventilatory control, methazolamide might be preferred for indications requiring the use of a carbonic anhydrase inhibitor, avoiding some of the negative side‐effects of acetazolamide.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.040
Threshold uncertainty score0.379

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.012
GPT teacher head0.294
Teacher spread0.282 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations11
Published2019
Admission routes2
Has abstractyes

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